Diabetic ketoacidosis

This page is for adult patients. For pediatric patients, see: diabetic ketoacidosis (peds)

Background

• 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.

Epidemiology

• Mortality rate approximately 2-5%

Pathophysiology

Defining features include hyperglycemia (glucose > 200mg/dl), acidosis (pH < 7.3), and ketonemia

Hyperglycemia

• Leads to osmotic diuresis and depletion of electrolytes including sodium, potassium, magnesium, calcium and phosphorus.
• Further dehydration impairs glomerular filtration rate (GFR) and contributes to acute renal failure
• Hypokalemia may inhibit insulin release

Acidosis

• Due to insulin deficiency -> lipolysis / accumulation of of ketoacids (represented by increased anion gap)
• Compensatory respiratory alkalosis (i.e. 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
• The initial serum values for electrolytes such as K+ may be higher than actual body stores
• Cation loss (in exchange for chloride) worsens metabolic acidosis

Clinical Features

• May be the initial presenting of an unrecognized T1DM patient
• OR symptoms/signs of inciting precipitant (e.g. history of med/dietary nonadherence, signs/symptoms of infection)
• Presenting features may include:
  • Polydipsia, polyuria (initially) or decreased urine output (as volume depleted)
  • Signs of dehydration (dry mouth, dry mucosa, etc.), hypotension
  • +/- Weight loss
  • Abdominal pain, nausea/vomiting
  • Tachypnea (Kussmaul's breathing)
  • Acetone or fruity smell on breath
  • Generally ill-appearance
  • Altered mental status, drowsiness with decreased reflexes
    • Cerebral edema increases mortality significantly, especially in children

Differential Diagnosis

Causes of DKA

• Insulin or oral hypoglycemic medication non-compliance (or insulin pump malfunction)
• Infection
• Cardiac Ischemia
• Intra-abdominal infections
• Steroid use
• ETOH Abuse
• Toxicologic exposure
• Pregnancy
• Hyperthyroidism
• GI Hemorrhage
• CVA
• PE
• Pancreatitis
• Renal Failure
• GI Bleed
• Alcoholic Ketoacidosis
• SGLT-2 inhibitors (euglycemic DKA)

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

Evaluation

Workup

Workup to confirm diagnosis and search for possible inciting causes (e.g. infection, ACS)

• CBC
• BMP
• Blood glucose
• Serum ketones (e.g. beta-hydroxybutyrate and/or acetone)
• Mag
• Phos
• VBG/ABG
• Consider ECG, urinalysis, chest X-ray, blood cultures

Diagnosis

Diagnosis is made based on the presence of acidosis (e.g. venous pH < 7.3 or HCO3 <18) and ketonemia (e.g. >3mmol/L BOH or ketonuria) in the setting of diabetes (e.g. glucose >200mg/dl)

Basic Laboratory Findings

• Blood Glucose
  • Capillary blood sugar >200mg/dL
  • Blood sugar may not be very elevated if there is impaired gluconeogenesis (eg liver failure, severe alcoholism) or patient is taking a SGLT-2 Inhibitor
• Elevated Anion Gap
  • Bicarb may be normal due to compensatory and contraction alkalosis so the elevated anion gap or ketonuria may be the only clues to the DKA
• Serum ketones
  • Beta hydroxybutyrate will be elevated

Blood Gas

No need to perform Arterial blood gas. Venous blood gas is sufficient

• Difference in pH from VBG vs ABG will be ±0.02pH units

Urinary analysis (ketonuria)

• Urinalysis may be a useful screening test early in DKA, if serum ketones not available
  • However, may give a false negative for ketones later in DKA, as acetoacetate is converted to beta-hydroxybutyrate the urinary ketones may turn negative

End Tidal CO2

Strongly consider capnography for respiratory distress

• ETCO2 can be used for bedside assessment of DKA in pts with glucose>550
  • An ETCO2 of ≥35 is 100% sensitive to rule out DKA
  • An ETCO2 of ≤21 is 100% specific to diagnosis DKA

Management

Algorithm for the management of diabetic ketoacidosis

• If the patient has an insulin pump, make sure it is shut off or disconnected

Volume Repletion

• Administer 20-30cc/kg lactated ringers 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
  • Increased systemic perfusion may transport insulin to previously unreached receptor sites, inhibiting ketogenesis
  • Increased renal perfusion promotes renal hydrogen ion loss
  • Use of LRs is preferred over NS ,
  • When blood sugar(BS) < 250-300 add a D10 infusion at an equal rate to the LR using a single IV line
  • Patients can eat and drink if mental status is intact

Electrolyte Repletion

• Potassium (most important!)
  • <3.5mEq/L:
    • Start potassium repleation: 20-30 mEq KCl to IVF/hr
    • Do not administer insulin (to avoid worsening of hypokalemia)
  • >3.5mEq/L and <5.5 mEq/L:
    • Start potassium repleation: 20-30 mEq KCl to IVF/hr
    • May start insulin (see below)
  • >5.5 mEq/L:
    • Hold potassium repletion and recheck electroltyes after initiaton of insulin (see below)
• Sodium
  • Hyponatremia
    • Correct for hyperglycemia
      • Na+ decreases by 1.6mEq/L for every 100mg/dL increase in glucose (ie pseudohyponatremia)
    • If truly hyponatraemic, start NS 250-500ml/hr
  • Hypernatremia
    • Consider Lactated Ringers
• Hypophosphatemia
  • <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
  • Mg<2.0mg/DL, start repletion:
    • 2g MgSO4 IV over 1h

Insulin Overview

• Check potassium prior to insulin treatment (see above)! Do not administer insulin until potassium supplementation is underway.
• A bolus dose is unnecessary and may contribute to increased hypoglycemic episodes
• If the patient comes in wearing an insulin pump, turn off the pump and remove the subcutaneous catheter.
• Expect BS to fall by 50-100mg/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

Long-Acting (Basal) Insulin

• Two main practices exist: 1) Close the anion gap, then start basal insulin 2-3 hours before stopping insulin infusion, 2) Early basal insulin
  • Potential benefits of early basal insulin (glargine or detemir) include protecting against erroneously stopping insulin infusion prematurely and eliminating the 2-3 hour waiting period of starting basal insulin while on IV infusion
• Early basal insulin:
  • Glargine 0.30 U/kg SQ x 1, OR
  • Determine total 24 hour home dose of basal insulin and deliver that q24 hours (e.g. patient's normal home dose of glargine)

Short-Acting Insulin

Intravenous Regimen (Short-Acting)

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.

• Initial infusion 0.1 to 0.14 units/kg/hr of insulin (or 0.05units/kg/hr per local protocol)
  • Fixed Rate Insulin Infusion has improved outcomes over Variable Rate
• 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 is begun
• Subcutaneous route (appropriate only for mild DKA and if able to eat and void urine; poor perfusion may hamper its absorption)

Subcutaneous Regimen (Short-Acting)

A subcutaneous (SC) regimen must use short acting insulin and follow either a 1hr or 2hr dosing protocol. Regular insulin is not effective. For patients who are euglycemic (glucose <250 mg/dl) at presentation (e.g. with mild gap), using standard insulin sliding scale instead of this regimen.

1hr Protocol

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

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
• Pitfalls of sodium bicarbonate therapy in DKA (outside of last ditch efforts in severe acidemia)
  • Paradoxical CSF acidosis
  • Hypokalemia from H+ and K+ shifts
  • Large sodium bolus
  • Cerebral edema
  • Shifts oxygen-hemoglobin dissociation curve to left, decreasing O2 delivery to tissues

Subsequent Management

Labs/Monitoring

• Glucose check Q1hr
• Chem 10 Q2r (then move to Q4hr)
• Check pH PRN based on clinical status (eval respiratory compensation)
• Check appropriateness of insulin dose Q1hr (see below)
• Corrected Electrolytes

Sliding Scale

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

Intubation

• Avoid intubation unless patient 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 patients
• See Intubation for more information

Disposition

• Admit to higher level care (usually ICU or step-down unit initially)
• Subsequent hospital discharge requires closing on anion gap and resolution of symptoms.
• Patients with mild DKA may be treated as outpatients if reliable, close follow-up available and underlying causes not requiring admission

Complications

• Cerebral Edema in DKA

See Also

• Diabetes mellitus (main)
• Evidence Review Sodium Bicarbonate in DKA
• Diabetic ketoacidosis (peds)
• Ketonemia
• Cerebral edema in DKA

External Links

• British Society for Paediatric Endocrinology and Diabetes - Paediatric Diabetic Ketoacidosis
• DDxOf: Management of DIabetic Ketoacidosis