Diabetic ketoacidosis

Background

Epidemiology

The mortality rate of DKA since the advent of insulin is approximately 2-5%

Pathophysiology

Definition

1. Hyperglycemia (glucose > 250 mg/dl)
2. Acidosis (pH < 7.3)
3. Ketosis

Hyperglycemia

• Leads to osmotic diuresis and depletion of electrolytes including sodium, magnesium, calcium and phosphorous.
• Further dehydration impairs glomerular filtration rate (GFR) and contributes to acute renal failure

Acidosis

• Due to lipolysis / accumulation of of ketoacids (represented by anion gap)
• Compensatory respiratory alkalosis
• Breakdown of adipose creates first acetoacetate leading to conversion to beta-hydroxybutyrate

Dehydration

• Causes Renin system activation in addition to the osmotic diuresis
• Cation loss (in exchange for chloride) worsens metabolic acidosis

Causes

1. Insulin or oral hypoglycemic medication non-compliance
2. Infection
3. Cardiac Ischemia
4. Intra-abdominal infections
5. Steroid use
6. ETOH Abuse
7. Drug abuse
8. Pregnancy
9. Hyperthyroidism
10. GI Hemorrhage

History

• Perform a thorough neurologic exam since Cerebral Edema increases mortality significantly especially in children
• Assess prior history of DKA or hyperglycemic episodes
• Is there associated infection?
• Is there another associated illnesses or risk factors
  • CVA, MI, PE, Pancreatitis, Renal Failure, GI Bleed, ETOH/drug use
• Has the patient been compliant with insulin use?
• Any recent medications started which could cause DKA

Workup

• CBC
• Chem 10
• UA
• Serum ketones: Beta-hydroxybutrate, acetoacetate
• hCG
• ECG
• VBG (equivalent to ABG for assessment of acid-base status)
  • Venous pH ~ 0.03 lower than arterial pH
  • Verify that respiratory compensation is as expected
• Chest xray is indicated if exam concerning for respiratory source of infection

Diagnosis

1. Blood Sugar>250
2. AG>12
3. Bicarb <15
4. pH <7.2
5. ketonemia and ketonuria

• BS may be lower if there is impaired gluconeogenesis (liver failure patients or severe alcoholics)
• Bicarb may be normal if there is concurrent alkalosis (e.g. vomiting)
  • In this case an elevated gap may be the only clue with anion gaps > 18 in severe ketonemia

Treatment

Volume Repletion

• Most important step in treatment since osmotic diuresis is the major driving force
• Administer 20-30cc/kg bolus during the first hour
• Most adult patients are 3-6L depleted
• Hyponatremia is a result of dilution. Start Normal Saline @ 250-500ml/hr
• If Hypernatremic then consider starting 1/2NS @ 250-500ml/hr after initial fluid bolus
• When blood sugar(BS) < 250 switch to D5_1/2NS@ 150-200 ml/hr(+/- KCl)

Insulin

• Check Potassium prior to insulin treatment!
• If K <3.5mEq/L do not administer insulin. If the potassium is < 5.5 mEq/L but > 3.5 mEq/L, then start potassium repletion along with your insulin.

• Insulin is required to stop the ketosis but a a bolus dose is unnecessary and may contribute to increased hypoglycemic episodes

• Expect BS to fall by 50-100 mg/dL per hr if you administer 0.1units/kg/hr of insulin
• Refractory hyperglycemia may be due to an associated infectious process contributing to the DKAn

IV Insulin Regimen:

1. Initial dose 0.1units/kg/hr of insulin
2. When BS <200mg/dL, reduce to 0.02-0.05 U/kg/hr IV OR give subQ 0.1 U/kg q2hr and switch IV fluids to D5_0.45%NS at 150cc/hr
3. Maintain BS between 150 and 200 until resolution of DKA
   1. May require IV fluids to be switched to D10_0.45%NS when BS <150mg/dL
4. Continue IV infusion for 2 hrs after subcutaneous insulin tx is begun
5. SubQ route (appropriate only for mild DKA)

Do not stop insulin infusion until AG normalized AND bicarb normalized

SubQ(SC) Insulin Regimen:

1hr Protocol

1. Initial dose SC Aspart: 0.3 units/kg body wt, followed by
   1. SC aspart insulin at 0.1 units/kg every hour
   2. When blood glucose <250 mg/dl (13.8 mmol/l), change IV fluids to D5<sub 0.45%NS and reduce SC aspart insulin to 0.05 units/kg/hr
   3. Keep glucose at 150mg/dl (11 mmol/l) until resolution of DKA.

2hr Protocol

1. Initial dose SC Aspart: 0.3 units/kg body wt, followed by
   1. SC aspart insulin at 0.2 units/kg 1 hr later followed by Q2hr dosing
   2. When blood glucose <250 mg/dl (13.8 mmol/l), change IV fluids to D5 0.45% saline and reduce SC aspart insulin to 0.1 units/kg/ 2hr
   3. Keep glucose at 150mg/dl (11 mmol/l) until resolution of DKA.

Electrolyte Repletion

1. Potassium repletion is most important
2. Sodium – Serum concentration diluted as a result of osmotic gradient of glucose pulling more water into extracellular space.
3. Hypophosphatemia: If < 1.0 mEq/L, start repletion.
   1. Severe hypophosphatemia can cause cardiac and respiratory dysfunction
4. Hypomagnesemia – All patients who are hypokalemic are hypomagnesemic. Replete together as long as kidney function intact.

Bicarb

• No benefit has been demonstrated from Sodium Bicarbonate therapy in acidosis cause by DKA
• Adding sodium bicarb to a patient's fluids requires to increase the respiratory rate to expel the converted CO₂
• Patients with DKA generally have maximally elevated respiratory rates and cannot increase. The bicarbonate administration then further increases the patient's acidoses.

DKA Refractory to Treatment

Assess for other causes of DKA

Labs/Monitoring

• Glucose check Q1hr
• Chem 10 Q4hr (initially Q2hr)
• Check pH prn based on clinical status (eval respiratory compensation)
• Check appropriateness of insulin dose Q1hr (see below)
• Corrected Electrolytes

Complications

Cerebral Edema

• • Almost all affected pts are <20yr
• Associated with initial bicarb level; not rate of glucose drop
• Symptoms:
• Headache
• Incontinence
• Mental Status Change / Seizure
• Treatment should be performed in conjunction with primary team recommendations
• Mannitol IV 1-2gm/kg OR
• 3% NS 5-10mL/kg over 30min
• Noncardiogenic pulmonary edema

Sliding Scale

Insulin Sliding Scale to be started once patient's DKA has resolved and eating a full diet.

See Also

• Diabetes (Main)
• DKA (Peds)
• EBQ:Sodium Bicarbonate use in DKA