4.3 Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State (HHS)

Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State (HHS)

Pathophysiology and Diagnostic Differentiation

Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State (HHS) are life-threatening endocrine emergencies representing opposite ends of the spectrum of severe insulin deficiency.

Diabetic Ketoacidosis (DKA)

DKA is characterized by uncontrolled lipolysis and ketogenesis. It occurs when an absolute or relative deficiency of insulin, combined with an elevation of counter-regulatory hormones (glucagon, catecholamines, cortisol, growth hormone), prevents glucose utilization. The body shifts to utilizing free fatty acids, which are metabolized in the liver into acidic ketone bodies (primarily beta-hydroxybutyrate and acetoacetate).

• Diagnostic Criteria:
  • Serum glucose > 250 mg/dL (can be lower in euglycemic DKA associated with SGLT2 inhibitors).
  • Arterial pH < 7.30.
  • Serum bicarbonate < 18 mEq/L.
  • Positive ketones in serum or urine.
  • Elevated anion gap > 10–12 mEq/L (Calculated as [Na+] - ([Cl-] + [HCO3-])).

Hyperosmolar Hyperglycemic State (HHS)

HHS occurs when there is sufficient residual insulin production to suppress lipolysis and ketogenesis, but not enough to facilitate glucose entry into tissues. Consequently, extreme hyperglycemia develops, leading to profound osmotic diuresis and severe dehydration.

• Diagnostic Criteria:
  • Serum glucose > 600 mg/dL.
  • Arterial pH > 7.30.
  • Serum bicarbonate > 18 mEq/L.
  • Minimal or absent ketonuria and ketonemia.
  • Effective serum osmolality > 320 mOsm/kg. Calculated as: 2 * [Na+] + (Glucose / 18).
  • Altered mental status (stupor, lethargy, or coma) directly proportional to the degree of serum hyperosmolality.

Fluid Resuscitation Protocol

Fluid deficits are massive (3–6 L in DKA; 8–10 L in HHS). Resuscitation must proceed in a structured, phased approach to restore intravascular volume while avoiding a rapid drop in serum osmolality, which can cause cerebral edema.

• Phase 1 (Intravascular Volume Expansion): Administer 0.9% Normal Saline or balanced crystalloids (e.g., Lactated Ringer's) at 15–20 mL/kg/hour (typically 1–1.5 L in the first hour).
• Phase 2 (Tailored Fluid Choice): Determine the corrected sodium level:
  • Corrected [Na+] = Measured [Na+] + 1.6 * ((Serum Glucose - 100) / 100)
  • If corrected sodium is high or normal: Administer 0.45% NaCl (half-normal saline) at 250–500 mL/hour.
  • If corrected sodium is low: Administer 0.9% NaCl at 250–500 mL/hour.
• Phase 3 (Dextrose Transition):
  • In DKA: When serum glucose falls below 250 mg/dL, transition the IV fluid to 5% Dextrose in 0.45% NaCl (D5 1/2 NS) at 150–250 mL/hour. This allows the continued insulin infusion required to clear ketones and close the anion gap while preventing hypoglycemia.
  • In HHS: When serum glucose falls below 300 mg/dL, transition to D5 1/2 NS to prevent rapid intracranial osmotic shifts.

Insulin and Electrolyte Management

Insulin therapy lowers blood glucose, inhibits lipolysis, and stops ketone production. However, it must be carefully timed with electrolyte correction:

• The Potassium Rule (CRITICAL):
  • Potassium < 3.3 mEq/L: DO NOT administer insulin! Insulin shifts potassium into cells, which will cause life-threatening hypokalemia and cardiac arrest. Hold insulin, administer IV potassium chloride at 20–40 mEq/hour until the serum potassium rises to >= 3.3 mEq/L.
  • Potassium 3.3–5.3 mEq/L: Administer insulin infusion and add 20–30 mEq of potassium chloride to each liter of IV maintenance fluids to maintain serum potassium between 4.0 and 5.0 mEq/L.
  • Potassium > 5.3 mEq/L: Administer insulin infusion. Do not add potassium to the IV fluids. Monitor serum potassium every 2 hours.
• Insulin Dosing: Initiate a continuous infusion of Regular Insulin at 0.1 units/kg/hour (e.g., 7 units/hr for a 70 kg patient). A bolus of 0.1 units/kg is optional but not required. The target rate of glucose decline is 50–75 mg/dL/hour. If the glucose does not fall by at least 50 mg/dL in the first hour, double the insulin rate.
• Sodium Bicarbonate: Routine administration is contraindicated as it worsens intracellular acidosis, shifts the oxygen-hemoglobin dissociation curve to the left, and increases the risk of cerebral edema. It is indicated only if the arterial pH is < 6.9. Administer 100 mmol sodium bicarbonate over 2 hours with 20 mEq KCl.

Pediatric DKA and Cerebral Edema

Pediatric patients are at high risk for cerebral edema, which carries a 20–25% mortality rate.

• Risk Factors: Rapid fluid administration, young age, new-onset diabetes, and severe acidosis.
• Clinical Presentation: Headache, bradycardia, lethargy, pupillary changes, and rising blood pressure (Cushing's triad).
• Treatment: Immediately administer Mannitol (0.5–1.0 g/kg IV over 20 minutes) or Hypertonic Saline (3% NaCl, 2.5–5 mL/kg over 10–15 minutes). Slow down the fluid administration rate by one-third.

Airway Management in Severe Acidosis

Intubating a patient in DKA is a high-risk procedure with high mortality. The patient’s respiratory system is compensating for severe metabolic acidosis via hyperventilation (Kussmaul breathing) to blow off CO2.

• The Hazard: During the period of induction and paralysis (apnea), the patient's PaCO2 will rapidly rise. A small increase in PaCO2 can cause the pH to drop catastrophically (e.g., from 6.95 to 6.80), leading to cardiac arrest.
• Management: Avoid intubation if at all possible. If intubation is mandatory, the transport clinician must set the ventilator to match the patient’s pre-intubation minute ventilation (high respiratory rate of 30–40 breaths/min and high tidal volume) to maintain a low PaCO2 (often 10–20 mmHg) until the acidosis resolves.

Diagnostic Comparison Table