DKA
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I now have comprehensive content from Harrison's, Goldman-Cecil, and Rosen's Emergency Medicine. Let me compile the full answer.
Diabetic Ketoacidosis (DKA)
Definition
DKA is defined by three core biochemical features - the "DKA triad":
- Hyperglycemia (glucose typically 250-600 mg/dL; can be lower in euglycemic DKA)
- Ketonemia/ketonuria (urine ketones 2+ or serum beta-hydroxybutyrate ≥3.0 mmol/L)
- Metabolic acidosis (arterial/venous pH <7.3; serum bicarbonate <18 mEq/L)
- Goldman-Cecil Medicine, p. 2484
- Harrison's Principles of Internal Medicine 22E, p. 3260
Pathophysiology
The central problem is insulin deficiency + counter-regulatory hormone excess (glucagon, cortisol, catecholamines, growth hormone). This drives three simultaneous processes:
1. Hyperglycemia pathway:
- Decreased glucose uptake by peripheral tissues
- Liver receives amino acids (from proteolysis) and glycerol/FFAs (from lipolysis) and converts them to glucose (gluconeogenesis) and glucose-6-phosphate (glycogenolysis)
- Osmotic diuresis exceeds renal threshold -> polyuria, dehydration, electrolyte loss
2. Ketogenesis pathway:
- Insulin deficiency activates hormone-sensitive lipase -> elevated free fatty acids (FFAs)
- Liver converts long-chain FFAs to acetoacetate, beta-hydroxybutyrate, and acetone
- Ketones are released into circulation faster than peripheral tissue can use them
- Result: high anion gap metabolic acidosis
3. Dehydration and electrolyte depletion:
- Osmotic diuresis causes urinary loss of water, Na+, K+, Mg2+, Ca2+, phosphorus
- Vomiting and poor oral intake compound fluid and electrolyte deficits
- Average deficits in severe DKA: water 70-120 mL/kg; Na+ 8-10 mEq/L; K+ 5-7 mEq/L
Important: Serum K+ is often normal or elevated at presentation despite profound total-body depletion, because acidosis drives K+ out of cells. This reverses rapidly with insulin therapy.
- Rosen's Emergency Medicine, p. 2542
Precipitants
| Most Common | Other |
|---|---|
| Infection (most frequent) | Acute pancreatitis |
| Inadequate insulin / nonadherence | Cerebrovascular accident |
| New-onset type 1 diabetes | Acute pulmonary embolism |
| Acute coronary syndrome | Alcohol intoxication |
| Unknown | Endocrinopathies (Cushing, thyrotoxicosis, acromegaly) |
| Drugs: SGLT-2 inhibitors, corticosteroids, clozapine, olanzapine, cocaine, sympathomimetics, thiazides |
- Goldman-Cecil Medicine, Table 210-11
Note: SGLT-2 inhibitors can cause euglycemic DKA - DKA with glucose <250 mg/dL. This diagnosis is easily missed because glucose is not markedly elevated.
Clinical Features
Symptoms (prodrome over hours to days):
- Polyuria, polydipsia
- Nausea, vomiting, anorexia
- Weakness, lethargy
- Nonspecific abdominal pain (can mimic acute abdomen)
- Reduced GI motility / paralytic ileus
Signs:
-
Dry skin and mucous membranes, reduced JVP, tachycardia, orthostatic hypotension
-
Kussmaul breathing - deep, rapid respirations (respiratory compensation for acidosis)
-
Fruity breath (acetone)
-
Depressed consciousness, sometimes frank coma (correlates with hyperosmolality)
-
Goldman-Cecil Medicine, p. 2484
Diagnosis / Lab Findings
| Parameter | DKA | HHS | Euglycemic DKA |
|---|---|---|---|
| Glucose | 250-600 mg/dL | 600-1200 mg/dL | 100-250 mg/dL |
| pH | 6.8-7.3 | >7.3 | <7.3 |
| Bicarbonate | <18 mEq/L | >18 mEq/L | <18 mEq/L |
| Beta-hydroxybutyrate | >3.0 mmol/L | <1.0 mmol/L | >3.0 mmol/L |
| Anion gap | Elevated | Normal to slightly elevated | Elevated |
| Osmolality | >300 mOsm/L | >300 mOsm/L | Normal |
| Sodium | 125-135 mEq/L | 135-145 mEq/L | Normal |
| Potassium | Normal to high | Normal | Normal to high |
- Harrison's Principles of Internal Medicine 22E, Table 416-7
Other findings:
- Elevated WBC (can be from acidosis itself, not just infection)
- Elevated hematocrit/Hb (hemoconcentration)
- Elevated serum amylase (usually non-pancreatic origin; can mimic pancreatitis)
- Prerenal azotemia (elevated BUN/Cr)
Ketone testing pitfall: Standard nitroprusside reagent strips detect acetoacetate and acetone but NOT beta-hydroxybutyrate. Since beta-OHB predominates in DKA, urine/serum dipstick may underestimate ketosis. Use bedside capillary ketone monitors (beta-OHB measurement) when available.
Severity Classification
| Mild | Moderate | Severe | |
|---|---|---|---|
| pH | 7.25-7.30 | 7.00-7.24 | <7.00 |
| Bicarbonate | 15-18 | 10-14 | <10 |
| Anion gap | >10 | >12 | >12 |
| Mental status | Alert | Alert/drowsy | Stupor/coma |
Management
1. Fluid Resuscitation (First Priority)
- Fluid deficit typically 3-5 L in adults (up to 5-10 L in severe cases)
- If hypovolemic shock: isotonic crystalloid (NS or Plasmalyte) as fast as possible (20 mL/kg bolus in children) until systolic BP ≥80 mmHg
- Standard adult approach: 1 L NS over first hour, then 2 L over 1-3 hours, followed by 0.45% NS (once hemodynamically stable)
- Fluid alone lowers glucose by ~18% through improved renal perfusion and glucose excretion
Evidence update: The SCOPE-DKA trial compared NS vs. Plasmalyte-148 in severe DKA; balanced crystalloids may restore physiologic parameters faster, but NS remains widely used.
2. Potassium Replacement
- Replace before starting insulin if K+ <3.5 mEq/L (otherwise worsening hypokalemia can cause fatal arrhythmia)
- Hold insulin until K+ ≥3.5 mEq/L
- If K+ 3.5-5.5: add 20-40 mEq/L to IV fluids
- If K+ >5.5: hold potassium, monitor every 2 hours
3. Insulin Therapy
- Regular insulin IV infusion is standard: typically 0.1 units/kg/hour (no bolus required in most protocols)
- Half-life of IV regular insulin is 3-10 minutes - always give by infusion, not repeated bolus
- Target: glucose fall of 50-75 mg/dL/hour
- When glucose drops to 250-300 mg/dL, switch IV fluid to D5-0.45%NS (or add dextrose) to prevent hypoglycemia and avoid rapid osmolarity shifts - but do NOT stop insulin until acidosis resolves (bicarbonate ≥18, anion gap normal, patient eating)
Recent meta-analysis: subcutaneous insulin protocols vs. IV infusion show similar outcomes in mild-moderate DKA, supporting use of SC insulin in selected patients [PMID: 39090718]. A 2026 systematic review also supports adding early subcutaneous basal insulin alongside IV insulin to reduce DKA recurrence [PMID: 41208563].
4. Sodium Bicarbonate
- Not routinely recommended
- Evidence shows it worsens hypokalemia, delays clearance of ketosis, causes paradoxical CSF acidosis, and may increase cerebral edema risk
- Consider only if pH <7.0 to prevent imminent cardiac arrest, or as a pre-intubation bolus to prevent cardiovascular collapse during RSI
5. Phosphate
- Routine replacement is not recommended (trials show no clinical benefit)
- Replace if severe symptomatic hypophosphatemia (e.g., respiratory muscle weakness)
6. Magnesium
- Often depleted in DKA (both from osmotic diuresis and insulin therapy)
- Deficiency can cause refractory hypokalemia, hypocalcemia, and fatal dysrhythmias
- Replete if hypomagnesemia is suspected (typical adult: 1-3 g IV)
7. Resolution Criteria
- pH ≥7.3
- Bicarbonate ≥18 mEq/L
- Anion gap normalizes
- Patient able to eat -> transition to subcutaneous insulin regimen
Complications
| Complication | Notes |
|---|---|
| Cerebral edema | Most feared complication; ~0.5-1% of pediatric DKA. Can develop as DKA resolves. Treat with mannitol immediately. Degree of acidosis/uremia is best predictor - not specific fluid or insulin regimen (PMID evidence from prospective study of 1255 pediatric patients) |
| Hypokalemia | Due to insulin therapy + fluid dilution; fatal arrhythmias possible |
| Hypoglycemia | Over-aggressive insulin therapy |
| Hypophosphatemia | Especially after extended treatment |
| ARDS | From aspiration or sepsis-related acute lung injury |
| Thromboembolic events | Especially in HHS; arterial and venous thromboses |
- Rosen's Emergency Medicine, p. 2545
- Harrison's Principles of Internal Medicine 22E, p. 3261
DKA vs. HHS - Key Differences
| Feature | DKA | HHS |
|---|---|---|
| Typical patient | Type 1 DM (also type 2) | Elderly type 2 DM |
| Insulin | Severely deficient | Partially present |
| Glucose | 250-600 mg/dL | >600 mg/dL (often >1000) |
| Ketosis | Prominent | Absent or mild |
| Acidosis | pH <7.3 | pH >7.3 |
| Osmolality | Moderately elevated | Markedly elevated (>320) |
| Fluid deficit | 3-5 L | 5-10+ L |
| CNS changes | Correlates with osmolality | Frank coma in up to 10% |
Special Situations
Pregnancy: DKA in pregnancy carries serious fetal risk even at lower glucose levels. A 2025 systematic review confirms adverse pregnancy outcomes following DKA [PMID: 40447103].
SGLT-2 inhibitor DKA: Euglycemic DKA - normal or near-normal glucose with ketonemia and acidosis. Easily missed. Patients may have used SGLT-2 inhibitors for type 2 DM, heart failure, or CKD. Require early dextrose addition when starting insulin.
Intubation: Avoid if possible. Patients have very high respiratory drive compensating for acidosis. If intubated, maintain hyperventilation to prevent worsening acidosis. Consider pre-intubation bicarbonate bolus if pH is critically low.
Sources: Goldman-Cecil Medicine; Harrison's Principles of Internal Medicine 22E; Rosen's Emergency Medicine 10E; PubMed PMIDs: 39090718, 41208563, 40447103.
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