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. Ketonuria or ketonaemia

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 increased anion gap)
• Compensatory respiratory alkalosis (ie tachypnea and hyperpnea - Kussmaul breathing)
• 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

• Note that DKA may be the initial presenting of an unrecognized T1DM patient
• Presenting signs/symptoms include altered mental status, tachypnea, abdominal pain
• Perform a thorough neurologic exam (cerebral edema increases mortality significantly, especially in children)
• Assess for possible inciting cause (esp for ongoing infection; see Differential Diagnosis section)

Physical

• Drowsiness
• Tachypnea (Kussmaul's breathing)
• Signs of dehydration
• Perform a thorough neurologic exam as cerebral edema increases mortality significantly, especially in children
• There may be signs from underlying cause (eg pneumonia)

Differential Diagnosis

Causes of DKA

• 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

Hyperglycemia

• Physiologic stress response (rarely causes glucose >200 mg/dL)
• Diabetes mellitus (main)
  • Nonketotic hyperglycemia
  • Hyperosmolar hyperglycemic state (HHS/HONC)
  • Diabetic ketoacidosis (adult)
  • Diabetic ketoacidosis (peds)
    • Cerebral edema in DKA
  • Diabetic foot infection
  • Diabetic peripheral neuropathy
• Hemochromatosis
• Iron toxicity
• Sepsis

Diagnosis

Workup

• CBC
• Capillary blood sugar >250mg/dL
  • Blood sugar may not be very elevated if there is impaired gluconeogenesis (eg liver failure, severe alcoholism)
• ABG (HCO3-, pH)
  • Bicarb may be normal due to compensatory mechanisms (eg tachypnea). In this case, an elevated anion gap or ketonuria may be the only clues to the DKA
• 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
• U/E/Cr (K+, Na+ and Cl- for anion gap)
• Serum ketones
• Urinary analysis (ketonuria)
  • Note that urine dipstick may give a false negative for ketones as it may not detect betahydroxybutyrate
• ECG
• Other investigations appropriate to suspected underlying cause (eg CXR, blood cultures)

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
• Consider LRs to avoid worsening acidosis with contributory hyperchloremic metabolic acidosis
• When blood sugar(BS) < 250 switch to Dextrose 5% 50-200 ml/hr (+/- KCl)

Insulin Overview

• Check Potassium prior to insulin treatment!
  • If potassium <3.5mEq/L, do not administer insulin
  • If potassium >3.5mEq/L and <5.5 mEq/L, 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

• Initial infusion 0.1units/kg/hr of insulin
• When BS <250mg/dL, halve the rate of infusion to 0.05units/kg/hr IV OR give subQ 0.1 U/kg q2hr and switch IV fluids to Dextrose 5% at 150cc/hr
• Maintain BS between 150 and 200mg/dL until resolution of acidosis
  • May require IV fluids to be switched to Dextrose 10% when BS <150mg/dL
• Continue IV infusion for 2 hrs after subcutaneous insulin tx is begun
• SubQ route (appropriate only for mild DKA)

Do not stop insulin infusion until AG normalized AND bicarb normalized, despite resolution of blood sugar. Aim of insulin regime is to correct the acidosis, not merely the hyperglycemia.

SubQ(SC) Insulin Regimen:

1hr Protocol

• Initial dose SC Aspart: 0.3 units/kg body wt, followed by
  • SC aspart insulin at 0.1 units/kg every hour
  • 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
  • Keep glucose at 150mg/dl (11 mmol/l) until resolution of DKA.

2hr Protocol

• Initial dose SC Aspart: 0.3 units/kg body wt, followed by
  • SC aspart insulin at 0.2 units/kg 1 hr later followed by Q2hr dosing
  • 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
  • Keep glucose at 150mg/dl (11 mmol/l) until resolution of DKA.

Electrolyte Repletion

• Potassium repletion is most important. Patients in DKA are almost always K+ depleted despite initially fairly normal K+. This is due to extracellular shift of K+ due to acidosis as well as insulin infusion, which increases uptake of K+ intracellularly.
• Sodium
  • Hyponatremia may be due to translational hyponatraemia
  • Na+ decreases by 1.6mEq/L for every 100mg/dL increase in glucose (ie pseudohyponatremia) **Correction of glucose will result in normalization of Na+
  • If truly hyponatraemic, start NS 250-500ml/hr
  • If Hypernatremic then consider starting half-strength NS 250-500ml/hr after initial fluid bolus
• Hypophosphatemia: If < 1.0 mEq/L, start repletion.
  • IV K2PO4 at 1mL/hour (contains 4.4meqK+ & 93mg phos)
  • Severe hypophosphatemia can cause cardiac and respiratory dysfunction
• 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
  • 2g MgSO4 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

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.

Intubation

• Avoid intubation unless pt cannot generate respiratory alkalosis compensation due to extreme fatigue
• Risks associated with intubation in DKA:
  • During sedation/paralysis, a rise in PaCO2 can decrease pH considerably
  • Severe gastroparesis in DKA creates a significant risk for aspiration
  • Strong DKA patients generally can achieve greater hyperventilation than mechanical ventilated pts

Complications

• Cerebral Edema in DKA

See Also

• Diabetes Mellitus (Main)