Diabetic ketoacidosis

Background

Epidemiology

The mortality rate of DKA 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 activation of RAAS in addition to the osmotic diuresis
• Cation loss (in exchange for chloride) worsens metabolic acidosis

Clinical Features

History & Physical

• Perform a thorough neurologic exam (cerebral edema increases mortality significantly, especially in children)
• Assess for possible inciting cause (see Differential Diagnosis section)

Studies

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

Differential Diagnosis

Causes

• Insulin or oral hypoglycemic medication non-compliance
• Infection
• Cardiac Ischemia
• Intra-abdominal infections
• Steroid use
• ETOH Abuse
• Drug abuse
• Pregnancy
• Hyperthyroidism
• GI Hemorrhage
• CVA
• PE
• Pancreatitis
• Renal Failure
• GI Bleed

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

Initial Management

Volume Repletion

• Administer 20-30cc/kg normal saline bolus during the first hour
  • Most important step in treatment since osmotic diuresis is the major driving force
  • Most adult patients are 3-6L depleted
• When blood sugar(BS) < 250 switch to D5_1/2NS@ 150-200 ml/hr(+/- KCl)

Insulin

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

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
   1. Serum concentration diluted as a result of osmotic gradient of glucose pulling more water into extracellular space
   2. Hyponatremia is a result of dilution. Start Normal Saline @ 250-500ml/hr
   3. If Hypernatremic then consider starting 1/2NS @ 250-500ml/hr after initial fluid bolus
3. Hypophosphatemia: If < 1.0 mEq/L, start repletion.
   1. IV K2PO4 at 1mL/hour (contains 4.4meqK+ & 93mg phos)
   2. 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 and if Mg<2.0 mg/DL or symptoms suggest hypomagnesemia
   1. 2g Mag sulf IV over 1h

Bicarbonate

• No evidence supports the use of sodium bicarb in DKA, with a pH >6.9
• However, no studies have been performed for patients with pH <6.9 and the most recent ADA guidelines recommend it for patients with pH <7.1

DKA Refractory to Treatment

Assess for other causes of DKA

Subsequent Management

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

Disposition

Admission: May require ICU

Sliding Scale

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

Complications

• Cerebral Edema in DKA

See Also

• Diabetes Mellitus (Main)