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

History

• Polyuria, polyphagia, polydipsia

• Headache, fatigue, decreased LOC

• Nausea/vomiting

• Abdominal pain

  • If abdominal pain does not improve as ketoacidosis improves, consider other pathologies for abdominal pain

Physical Examination

• Dehydration, postural hypotension, tachycardia, tachypnea

• Resp: Kussmaul respiration, acetone-odoured (fruity) breath

• Abdo: Diffuse abdominal tenderness 

• Neuro: LOC, pupils

Diagnosis

• Suspect in hyperglycemia and symptoms

  • DKA

    • Develops over hours

    • Typically, anion gap metabolic acidosis (although vomiting may cause a normal pH and normal bicarb)

      • Arterial/venous pH ≤7.3

      • Serum bicarbonate ≤15 mmol/L

      • Anion gap >12 mmol/L 

    • Positive ketones in serum and/or urine (acetoacetate)

      • β-hydroxybutyrate level >1.5 mmol/L has a sensitivity of 98-100% and specificity of 78.6-93.3% 

      • Ketosis differential:

        • DKA

        • Alcoholic ketoacidosis

        • Starvation ketoacidosis

        • Isopropyl alcohol ingestion

    • Plasma glucose usually ≥14.0 mmol/L

      • Can be euglycemic DKA (eg. SGLT2, pregnancy, chronic pancreatitis, bariatric surgery), will need immediate dextrose infusion

  • HHS

    • Develops over days

    • Plasma glucose >33

    • pH >7.3, Bicarb >15, no ketones

    • Serum osmolality >320mOsm/kg

• Trigger: 

  • Infection (30%)

  • New diagnosis of diabetes (25%)

  • Insulin non-adherence (20%)

  • Infarction (ACS, CVA, mesenteric ischemia)

  • Alcohol

  • Trauma

  • Medications (eg. glucocorticoids, diuretics, atypical antipsychotics)

  • Abdominal pathology

  • Pregnancy

Investigations

• Blood gas, including lactate

  • Anion gap = [Na+] – [Cl−] – [HCO3−], if >10-12mEq/L consider elevated anion gap differential

• Serum osmolality (HHS)

• CBC, Chem-10 (Ca, Mg, Phos)

• LFTs, albumin, CK

• bhCG

• Capillary Ketones

• Serum ketones +/- serum beta-hydroxybutyrate level

• Urinary ketones (more false negatives and false positives)

• Consider

  • Lipase (note can be increased by DKA)

  • Infectious work-up

    • UA

    • Blood/urine cultures

    • CXR

  • EKG

    • Troponin (only if EKG suggests ischemia)

  • Serum ketons (β-hydroxybutyrate) if diagnosis unclear

Treatment

• ABC, vitals

  1. Fluid resuscitation

     • Bolus

       • NS 10mL/kg (or 1L) bolus IV

       • If persistent tachycardia or hypoperfusion, repeat until euvolemic (HR<100)

     • Maintenance

       • See table below for rates in pediatrics

       • In adults, eg. 0.9% NS 250mL/h x 4-6h then 0.45% NS 250mL/h (to avoid hyperchloremic metabolic acidosis

     • Add IV dextrose when serum glucose <14.0 mmol/L (maintain glucose 12-14)

       • eg. D5W 0.5%NS or D5W 0.45%NS

       • If glucose <4, provide 1 amp of D50 and increase dextrose infusion

  2. Avoidance of hypokalemia

     • Add KCl 40 mmol/L when serum K<5.0 mmol/L and patient has urinated (cardiac monitoring needed, caution in renal failure- ensure urine output)

       • Consider oral potassium 

       • Magnesium/phosphate replacement as needed

  3. Insulin administration (avoid initially in HHS)

     • Hold insulin if K<3.3

     • If mild-moderate DKA (pH 7.1-7.29, HCO3 5-14.9)

       • After one hour of fluids, Humalog 0.15 Units/kg/dose (or 10 units) q2h

     • If severe (pH<7.1, HCO3<5)

       • After one hour of fluids, Humulin R infusion of 0.1 units/kg/h (0.05 units/kg/h for HHS)

       • If glucose does not fall by 3mmol/L in first hour, check IV access and if normal consider doubling insulin

       • Bolus may increase hypoglycemic events without clinical benefits

       • If hypoglycemia give more glucose, do not stop insulin (to avoid more ketoacidosis)

  4. Monitor for cerebral edema (Risk in severe DKA, young age <5yo and new onset diabetes)

     • Suspect cerebral edema if sudden headache, altered LOC and lethargy, irritability in young children, Cushing's triad (high BP, low HR, low RR)

       • Manage ABC, raise head of bed 30 degrees, restrict fluid

       • Consider mannitol 0.25-0.5g/kg IV over 30 mins OR hypertonic 3% NS 5-10mL/kg over 30 mins

  5. Search for precipitating cause (infection, drugs, thyrotoxicosis, adherence to medication, new diabetes, MI, stroke)

Monitor

• Repeat serum glucose q1h

• Repeat VBG (pH, electrolytes), plasma osmolality (for HHS) q2-4h until stable

  • Anion gap = [Na+] – [Cl−] – [HCO3−]  (may consider adjust for albumin with other more complicated formulas)

• May consider monitoring osmolality

  • • Measure or calculate osmolality (2 [Na+] + [glucose] + [urea] in mmol/L)

      • Aim for gradual decline, especially in patients under 40 years old (eg. 3 mmmol/kg/hr or 20mOsm/kg/day)

        • If osmolality increase

          • Fluid balance inadequate, increase rate of 0.9%NS

          • Fluid balance adequate, consider switch to 0.45%NS

        • If osmolality decreasing >8mosmol/kg/h, consider reducing IV fluids

Goal

• Avoid overly aggressive therapy which will cause complications (hypokalemia, cerebral edema)

• Most patients with DKA (especially those with HHS) probably need admission and observation,

• DKA: 

  • Normalization of the plasma anion gap <12 mEq/L

  • Ketoacidosis resolved

  • Normalization of bicarbonate

  • Glucose controlled <14 mmol/L

• HHS: Mentally alert, and osmolality <315 mOsmol/kg

• Patient eating and ideally hungry

  • Received full daily dose of long-acting insulin >2 hours (Consider SC insulin regimen once glucose <11.1)